Lung pharmacokinetics of lipid-extracted natural bovine surfactants of different composition and currently used in neonatology were studied in 568 airway specimens from 23 consecutively admitted, small preterm neonates (gestational age, 26.7 +/- 0.3 wk) who were mechanically ventilated for 5 to 7 d in a tertiary care center. In six infants who were mechanically ventilated only, no changes in phospholipid quantity or composition were noted. The other infants were randomly assigned to two groups that received the natural surfactants Survanta or Alveofact, respectively. In the Survanta group (n = 6), exponential decreases were observed in the percentage of phosphatidylglycerol (PG) and sphingomyelin (Sph), while phosphatidylinositol (PI) remained low. In Alveofact-treated neonates (n = 8), PG also decreased exponentially, whereas PI increased linearly during the first week of life to values equivalent to those in infants not treated with surfactant. The exponential disappearance of PG and Sph from repetitive airway samples was utilized to calculate an apparent endogenous pool size, for the time before surfactant treatment, of about 20 mg phospholipids/kg body weight (n = 14). The apparent half-life of PG in the Alveofact group (43 +/- 11 h) was shorter than in the Survanta-treated infants (105 +/- 23 h, p < 0.01), and a similar value was obtained for Sph (97 +/- 21 h, n = 6). There was no correlation between PG or Sph half-life and the amount of surfactant applied. These data for human neonates show a dependence of surfactant clearance and metabolism on the type of bovine surfactant preparation administered.